Method for configuring an arteriovenous fistula

ABSTRACT

An embodiment of the invention relates to a method of configuring blood vessels at an anastomosis, the method comprising: ensheathing a segment of a transected first blood vessel in a lumen of a sleeve so that an open end of the segment protrudes from a sleeve end; suturing edges of an incision made in a second blood vessel to the open end of the first blood vessel to create an anastomosis; and sliding the sleeve along the first blood vessel to position the sleeve at the anastomosis.

RELATED APPLICATIONS

The present application is a continuation under 35 U.S.C. 120 of U.S.application Ser. No. 14/937,889 filed Nov. 11, 2015, which is adivisional under 35 U.S.C. 120 of U.S. application Ser. No. 14/611,256filed Feb. 1, 2015, which is a continuation under 35 U.S.C. 120 ofPCT/IB2013/056322 filed on Aug. 1, 2013, which claims benefit under 35U.S.C. 119(a)-(d) from International Application PCT/EP2012/065078 filedAug. 1, 2012 as well as benefit under 35 U.S.C. § 119(e) from U.S.Provisional Application 61/679,016 filed Aug. 2, 2012 and U.S.Provisional Application 61,679,332 filed Aug. 3, 2012. The contents anddisclosures of each of these prior applications are incorporated hereinby reference in their entirety.

FIELD

The current disclosure relates to configuring blood vessels in a regionof a fistula through which blood flows from one to the other of theblood vessels.

BACKGROUND

Patients with end stage renal disease undergo frequent hemodialysis toremove toxins from the blood and maintain appropriate homeostasis. Indialysis, blood is withdrawn from a vascular access, purified, andreturned to a vein or a synthetic graft. The two most common formsdesigned to enable long-term vascular access in chronic hemodialysispatients are the native arteriovenous (AV) fistula and an AV shunt.

In the AV fistula method, openings are created in an artery and vein,usually in the arm above or below the elbow. The borders of the openingsare attached to form an anastomosis at which the vein is joined to theartery and provide a common passageway, conventionally referred to as afistula, through which blood flows directly from the artery to the vein.The arterial blood pressure, being higher than the venous pressure,together with the supra-physiological flow rates, eventually enlargesthe vein and a “mature” and a functioning vascular access is created 2-4months post procedure. The mature vascular access enables sufficientblood flow rate, effective dialysis procedure and the accommodation of acannula or large needles.

Hemodialysis vascular access dysfunction is a contributing factor tomorbidity in hemodialysis patients. According to Roy-Chaudhury et al.,“Vascular access in hemodialysis: issues, management, and emergingconcepts” (in Cardiology Clinics 23, 2005: 249-223) there are severalcauses of failures of vascular access procedures. Roy-Chaudhury et al.identifies two main causes of such failure in AV fistulae as maturationfailure and early venous stenosis, both are caused by development ofneointimal hyperplasia which includes thickening of the tunica media andthe tunica intima (a smooth muscle wall and endothelial layer in thevessel) due to inward proliferation of cells.

Maturation failure and early venous stenosis may be caused by thedevelopment of a juxta-anastomotic stenosis due to the neointimalhyperplasia in propinquity to the artery-vein anastomosis. According toRoy-Chaudhury et al., an initiating event in the pathogenesis of venousstenosis in AV dialysis is hemodynamic stress, especially in regions oflow shear stress and turbulence in the vicinity of the fistula. Anotherinitiating event is the high wall tension to which the vein graft isexposed. Under normal physiological conditions, the pressure in thevenous circulation is 3-5 mmHg. After fistula creation, the meanpressure in the vein is 100 mmHg. Unlike arteries, veins have relativelythin wall with thin muscularis layer. As a compensation reaction, whiletrying to adapt to the “new” physiological conditions and highpressures, the vein wall thickens in an attempt to reduce the suddenhigh wall tension. The pathological process of wall thickening isconsidered the seed of intimal hyperplasia and vein stenosis.

SUMMARY

An aspect of an embodiment of the invention relates to providing anapparatus or a system, also referred to as a “fistula join”, to provideand maintain a desirable configuration of native blood vessels or anative blood vessel and an artificial blood conduit in the vicinity of afistula through which blood flows from one to the other of the bloodvessels or between the conduit and the native blood vessel. Forconvenience of presentation a native blood vessel and a blood conduitare generically referred to as a blood vessel.

As used herein, the “fistula” refers to the plane of the opening throughwhich the blood from a first blood vessel flows to a second bloodvessel. The fistula may be, for example, created through the process ofanastomosis. The “vicinity of the fistula”, as used herein, refers to atleast the portion of the first and second blood vessels apposed to,enclosed within, ensheathed within or within the lumen of a fistula joinor components thereof.

According to an embodiment of the invention, a fistula join comprises acoupler that couples to a first of a pair of blood vessels joined at afistula and a restrictor sleeve (alternatively referred to herein as a“sleeve”) that ensheathes a second of the pair of blood vessels. Thecoupler optionally comprises a mount and an adapter. The mount seats onthe first blood vessel and surrounds at least a portion of the firstblood vessel. The mount may comprise at least one brace that can beclosed to prevent the coupler, once seated on the first blood vessel,from lifting off from the first blood vessel. Optionally, the mount hasa shape reminiscent of a saddle and the at least one brace comprises twoopposing braces that may be joined to “strap” the mount and therebysecure the coupler to the first blood vessel. The adapter extends fromthe mount and is configured to mate and fasten to the restrictor sleevethat ensheathes the second blood vessel. The adapter may have a collarlike shape that fits over or inside the restrictor sleeve. Optionally,the restrictor sleeve is integrally formed as an extension of theadapter.

In an embodiment of the invention, the adapter is configured to hold therestrictor sleeve and thereby the second blood vessel in the vicinity ofthe fistula substantially at a desired acute angle relative to adirection along which the portion of the first blood vessel to which thecoupler is attached extends. The desired acute angle may hereinafter bereferred to as a “fistula join angle”, or a “join angle”. The couplermay be configured to constrain the portion of the first blood vessel towhich it is mounted, or the portion of the second blood vessel in thevicinity of the fistula that is substantially contained within the lumenof the adapter, to a desired shape, hereinafter also referred to as a“first constrained shape”. The restrictor sleeve may be configured tolimit strain or wall tension generated by blood pressure in the portionof the second blood vessel that the sleeve ensheathes. Additionally, therestrictor sleeve may be configured to constrain the second blood vesselportion to a desired shape or size. The desired shape or size of theensheathed blood vessel may hereinafter be referred to as a “secondconstrained shape”.

In an embodiment of the invention, the fistula join is configured toprovide a desired flow pattern of blood through the fistula and inregions of the first and second blood vessels in the vicinity of thefistula. Configuring the fistula join may comprise configuring any oneor combination of at least two of the coupler mount, the coupler adapteror the restrictor sleeve. Configuring the fistula join may be performedto configure any one or any combination of two or more of the joinangle, the first constrained shape, and the second constrained shape. Inan embodiment of the invention, the fistula join may be configured toenhance laminar flow of blood through the fistula and/or in at least oneof the first and second blood vessels in the vicinity of the fistula.Optionally, the fistula join is configured to moderate blood pressure inthe first or second blood vessel.

In an embodiment of the invention, the fistula is an arteriovenousfistula that provides direct blood flow from an artery to a vein and thefistula join is adapted to configure the vein and artery in the vicinityof the fistula. The first blood vessel, to which the coupler, optionallyreferred to as the “artery coupler”, is attached, is the artery,optionally referred to as the “fistula artery”. The second blood vesselthat the restrictor sleeve ensheathes is the vein, optionally referredto as the “fistula vein”. The restrictor sleeve may be referred to as a“venous restrictor sleeve”. The fistula join comprising the arterycoupler and the venous restrictor sleeve may be referred to as anarteriovenous fistula join.

In an embodiment of the invention, the join angle of the arteriovenousfistula join is between about 20° and about 60°.

In an embodiment of the invention, the venous restrictor sleeve, whichis oriented at the join angle, may ensheathe a length of from about 10mm to about 30 mm of the vein. Optionally the restrictor sleeve has aconstant cross section. The restrictor sleeve may have a cross sectionthat changes as a function of distance along the sleeve. Optionally, thecross section increases with distance along the vein from the fistula.The diameter of the restrictor sleeve outlet distal from the fistula maybe larger than the diameter of the restrictor sleeve inlet proximal tothe fistula. The ratio of the outlet diameter to the inlet diameter maybe between about 1.3 and about 1.5. Optionally, the inlet may assume asubstantially circular cross section having an internal diametersubstantially equal to or greater than an external diameter of the firstblood vessel. Optionally, the restrictor sleeve has a mixedconical/cylindrical shape, having a conical segment proximal to thefistula having a cross section that increases with distance from thefistula and a cylindrical segment distal from the fistula having aconstant cross section. Optionally, the conical segment may comprisebetween about 50% and about 80% of the restrictor sleeve along itslongitudinal axis, with the remainder of the restrictor sleeve beingcylindrical in shape. Optionally, the conical segment may be betweenabout 10 mm and about 25 mm in length.

Arteriovenous fistula joins characterized by join angles and restrictorsleeve dimensions in accordance with an embodiment of the invention mayprovide advantageous Reynolds numbers and corresponding improved laminarblood flow through a fistula at an anastomosis between an artery and avein. In an embodiment of the invention, the Reynolds number is lessthan about 1500.

Another aspect of an embodiment of the invention relates to a method forproviding external support to an arteriovenous fistula comprising thesteps of: providing a fistula join comprising a coupler connected to arestrictor sleeve; transecting a vein and selecting the vein segmentleading to the heart; passing the vein segment completely through thelumen of the fistula join so that the transected end of the vein segmentprotrudes from the coupler; anastomosing the protruding end of said veinsegment to the side of an artery to create an arteriovenous junction;and passing the fistula join along the vein segment so that coupler isin contact and nested upon a portion of the artery adjacent to orsurrounding the fistula.

There is therefore provided in accordance with an embodiment of theinvention, apparatus for configuring first and second blood vesselsconnected by an anastomosis at a fistula, the apparatus comprising: acoupler that seats on and couples to the first blood vessel; and asleeve connected to the coupler that ensheathes and holds a portion ofthe second blood vessel in the vicinity of the fistula so that an acutejoin angle formed between the first and second blood vessels at thefistula is greater than about 20°. Optionally, the join angle is lessthan about 60°. Additionally or alternatively, the sleeve has a crosssection that is a function of distance along the sleeve from thecoupler.

There is further provided in accordance with an embodiment of theinvention, apparatus for supporting first and second blood vesselsconnected by an anastomosis at a fistula, the apparatus comprising: acoupler that seats on and couples to the first blood vessel; and asleeve connected to the coupler that ensheathes a portion of the secondblood vessel in the vicinity of the fistula and has a cross section thatis a function of distance along the sleeve from the coupler.

In an embodiment of the invention, the sleeve assumes a substantiallycircular cross section proximal to the fistula having an internaldiameter substantially equal to or greater than an external diameter ofthe first blood vessel.

In an embodiment of the invention, the cross section of the sleeveincreases as a function of distance from the coupler along the sleevefor at least a first portion of the sleeve length, beginning from thesleeve opening proximal to the fistula. Additionally or alternatively,the first portion is greater than or equal to about 50% of the totalsleeve length. The first portion is optionally greater than or equal toabout 60% of the total sleeve length. The first portion is optionallyless than or equal to about 80% of the total sleeve length. Additionallyor alternatively, the first portion is equal to or greater than about 10mm in length. The first portion is optionally equal to or greater thanabout 15 mm in length. The first portion is optionally less than orequal to about 20 mm in length. Additionally or alternatively, thediameter at the larger opening of the sleeve is greater than or equal toabout 1.3 times the diameter at the smaller opening of the sleeve.Optionally, the sleeve is greater than or equal to about 1.4 times thediameter at the smaller opening of the sleeve. Optionally, the diameterat the larger opening of the sleeve is less than or equal to about 1.5times the diameter at the smaller opening of the sleeve. Additionally oralternatively, the sleeve has a second portion that extends from an endof the first portion to an end of the sleeve and has a substantiallysame cross section at each point along its length.

In an embodiment of the invention, the sleeve has a length equal to orgreater than about 15 mm. Optionally, the sleeve has a length equal toor greater than about 20 mm. Optionally, the sleeve has a length equalto or greater than about 25 mm. Optionally, the sleeve has a lengthequal to or less than about 30 mm.

In an embodiment of the invention, the coupler comprises a brace thatcan be closed to prevent the coupler from lifting off from the firstblood vessel.

In an embodiment of the invention, the coupler is operable to impose arounded contour to at least a portion of the first or second bloodvessel apposed to the coupler. Optionally, the coupler is operable toimpose a rounded contour to the portion of the first or second bloodvessel at the acute angle formed by the junction of the first and secondblood vessels.

In an embodiment of the invention, the first blood vessel is an artery.The artery is optionally a brachial artery or a radial artery.

In an embodiment of the invention, the second blood vessel is a vein.The vein is optionally a cephalic vein.

There is further provided in accordance with an embodiment of theinvention, a method of configuring blood vessels at an anastomosis, themethod comprising: making an incision having edges in a first bloodvessel; transecting a second blood vessel to provide a blood vesselsegment having an open end; ensheathing the segment in a sleeve so thatthe open end protrudes from the sleeve; suturing the open end to edgesof the incision to form a fistula; sliding the sleeve along the secondblood vessel to position the sleeve at the anastomosis; and coupling thesleeve to the first blood vessel so that the sleeve configures a portionof the second blood vessel that extends from the fistula. Optionally,the incision in the first blood vessel is made before transecting thesecond blood vessel. Optionally, the incision in the first blood vesselis made after transecting the second blood vessel. Optionally, theincision in the first blood vessel is made after ensheathing the segmentof the second blood vessel in the sleeve.

Additionally or alternatively, coupling the sleeve comprises suturing orgluing a portion of the sleeve to the first blood vessel.

Additionally or alternatively, coupling the sleeve comprises seatingonto the first blood vessel a coupler previously connected to the end ofthe sleeve proximal to the fistula. Optionally, coupling the sleevefurther comprises closing a brace incorporated into the coupler aroundthe first blood vessel.

In the discussion, unless otherwise stated, adverbs such as“substantially”, “approximately” and “about” modifying a condition orrelationship characteristic of a feature or features of an embodiment ofthe invention, are understood to mean that the condition orcharacteristic is defined to within tolerances that are acceptable foroperation of the embodiment for an application for which it is intended.Unless otherwise indicated, the word “or” in the specification andclaims is considered to be the inclusive “or” rather than the exclusiveor, and indicates at least one of, or any combination of items itconjoins.

This Summary is provided to introduce a selection of concepts in asimplified form that are further described below in the DetailedDescription. This Summary is not intended to identify key features oressential features of the claimed subject matter, nor is it intended tobe used to limit the scope of the claimed subject matter.

BRIEF DESCRIPTION OF FIGURES

Non-limiting examples of embodiments of the invention are describedbelow with reference to figures attached hereto that are listedfollowing this paragraph. Identical structures, elements or parts thatappear in more than one figure are generally labeled with a same numeralin all the figures in which they appear. A label labeling an iconrepresenting a given feature of an embodiment of the invention in afigure may be used to reference the given feature. Dimensions ofcomponents and features shown in the figures are chosen for convenienceand clarity of presentation and are not necessarily shown to scale.

FIGS. 1A-B schematically illustrate an arteriovenous junction with afistula in an arm;

FIGS. 2A-B schematically illustrate an exemplary fistula join having acoupler and a restrictor sleeve for modifying an arteriovenous fistula,in accordance with some embodiments of the present invention;

FIG. 3 schematically illustrates an exemplary fistula join having acoupler and a restrictor sleeve, in accordance with some embodiments ofthe present invention;

FIG. 4A schematically illustrates, in perspective views, an exemplarycoupler, in accordance with some embodiments of the present invention;

FIG. 4B schematically illustrates, in perspective views, an exemplarycoupler, in accordance with some embodiments of the present invention;

FIG. 4C schematically illustrates, in perspective views, an exemplarycoupler, in accordance with some embodiments of the present invention;

FIGS. 5A-E schematically illustrate steps of a method for providingexternal support to an arteriovenous fistula in accordance with someembodiments of the present invention;

FIGS. 6A-B show the visualization of blood flow at a simulatedarteriovenous junction, characterized by different vein/artery diameterratios;

FIGS. 7A-B show the visualization of blood flow at a simulatedarteriovenous junction, characterized by different vein/artery diameterratios;

FIGS. 8A-C show the visualization of blood flow in a simulatedarteriovenous junction, characterized by different sizes of an initialconical segment in the vein; and

FIG. 9 shows the visualization of blood flow in a simulatedarteriovenous junction in a conventional configuration.

DETAILED DESCRIPTION

The present invention, in some embodiments thereof, relates to externalvascular supports and in particular to external supports forarteriovenous junctions. In the following detailed description, thecomponents of an exemplary arteriovenous junction and features of itsmaturation are schematically illustrated in FIGS. 1A-B and discussedwith reference to those figures. Examples of a fistula join having acoupler and/or a restrictor sleeve in accordance with embodiments of theinvention are schematically illustrated in FIGS. 2A-B and FIG. 3 , anddiscussed with reference to the figures. Examples of a coupler inaccordance with embodiments of the invention are shown in perspectiveviews in FIGS. 4A-C and discussed with reference to the figures. Stepsof a method for providing external support to an arteriovenous junctionusing a fistula join in accordance with embodiments of the invention areshown in FIGS. 5A-E and discussed with reference to the figures. Imagesof computer simulations of blood flow from an artery through a fistulato a vein in regions of anastomosis joining the artery and vein areshown in FIGS. 6A-B and FIGS. 7A-B, and discussed with reference to thefigures. Images of computer simulations of blood flow from an arterythrough a fistula to a vein, with the initial vein segment proximal tothe fistula shaped as various combinations of cone-like andcylinder-like segments, are shown in FIGS. 8A-C and discussed withreference to the figures. An image of a computer simulation of bloodflow from an artery through a fistula to a vein in a conventionalarteriovenous junction is shown in FIG. 9 .

The following embodiments may be described in the context of exemplaryexternal support systems for arteriovenous junctions that are preparedin patients to facilitate hemodialysis, for convenience of descriptionand understanding. However, embodiments of the invention are not limitedto the specifically described devices and methods, and embodiments maybe adapted to various clinical applications without departing from theoverall scope of the invention. For example, devices and related methodsincluding concepts described herein may be used for preventing and/ortreating intimal hyperplasia or remodeling in other manmade anatomicaljunctions, including end-to-side, end-to-end or side-to-sideanastomoses, in vasculatures or other organs.

FIGS. 1A-B schematically illustrate an arteriovenous junction, AVJ,forming a fistula FS in an arm. Arteriovenous junction AVJ is surgicallyprepared by the procedure of anastomosis, where the open end of vein VNis connected to a side of an artery AR having an arteriotomy, thusproviding a common passageway, conventionally referred to as a fistula,through which blood flows directly from artery AR to vein VN. As usedherein, in the context of an arteriovenous junction, fistula FS refersin particular to the opening of the common passageway at the side ofartery AR. It will be appreciated that the location of the fistula FSmay be independent of the precise location of the junction betweenarterial tissue and venous tissue. Depending on the particulars of theanastomosis procedure and/or how the vascular walls heal and mature overtime, the vascular wall at the fistula may be arterial, venous, or acombination thereof. Where vein VN joins artery AR at arteriovenousjunction AVJ at an angle other than a right angle, the fistula FS may beshaped substantially as an ellipse. Typically, but not necessarily, theminor axis of the ellipse may be substantially equal to a diameter ofartery AN at or in the vicinity of the fistula.

FIG. 1A shows the arm with fistula vein VN in a mature stage. Fistulavein VN connected to artery AR through fistula FS matures over monthsfollowing the anastomosis procedure. Fistula vein VN, once fullydeveloped, becomes enlarged and suitable for introductions of needles orcannulae for connecting with an external hemodialysis system used forarterial extraction of blood with waste products and venous return offiltered blood. However, concomitant with the maturation of fistula veinVN, stenosis ST may also develop, reducing blood flow and bloodpressures into fistula vein VN.

FIG. 1B shows an enlarged view of arteriovenous junction AVJ withfistula FS at an earlier stage, for example immediately followingfistula FS formation through anastomosis AN of a fistula vein VN with anartery AR. Blood flow FL flowing downward via artery AR now enters,completely or partly, into fistula vein VN via fistula FS. At thisstage, stenosis is absent. Fistula vein VN may be somewhat expanded,even at initial stages prior to fistula vein maturation, due to the higharterial pressure it now houses.

FIGS. 2A-B schematically illustrate an exemplary fistula join system100. Fistula join 100 includes a coupler 120. Optionally, fistula join100 further includes a restrictor sleeve 110 connectable to coupler 120.In certain alternative embodiments, fistula join 100 may includerestrictor sleeve 110 without coupler 120.

Coupler 120 includes a mount 124 having a first shape, an adapter 123having a second shape, and an intermediate portion 121 shaped such thatit gradually alters in shape from the first shape to the second shape. Alumen 122 passes through coupler 120 and is configured to directlycommunicate with lumen 112 when coupler 120 and restrictor sleeve 110are connected correctly.

Mount 124 is shaped to nest over a rounded artery portion AR adjacentarteriovenous junction AVJ. In order to substantially coincide overartery portion AR, mount 124 includes a saddle-like shape sized toaccommodate artery AR diameter along a substantial length, therebyproviding sufficient support to maintain a desirable configuration ofthe fistula at the arteriovenous junction, as well as the portions ofthe anastomosed vein and artery in the vicinity of the fistula. Mount125 may also provide sufficient support to secure a restrictor sleeve110 at a determined alignment, orientation or angle.

Mount 124 may further include a brace 125, which may for example includetwo legs configured to be closable in order to prevent coupler 120, onceseated on artery AR, from lifting off from artery AR. The legs may beelastic and form a non-stressed ring-like shape having a chosendiameter, which could be substantially the same as of artery AR,slightly larger or slightly smaller. The closing of brace 125 may besecured with or without additional suturing or bonding. Additionally,brace 125 may be operable to deform the geometrical configuration of thefistula and the surrounding vascular wall, which deformation may beoperable to improve blood flow at or near the deformation.

Adapter 123 extends from mount 124 and is connectable with restrictorsleeve 110. Adapter 123 may comprise a cylindrical shape enclosing adiameter being equal to or greater than the external diameter of afistula vein segment inserted therein. The end of the cylindrical shapemay have a collar-like shape that fits over or inside inlet 114 ofrestrictor sleeve 110. Adapter 123 may be connectable with inlet 114 ofrestrictor sleeve 110, optionally, by means of one or more of:mechanical tension, a mechanical interlocking mechanism, welding,bolting, snap-locking, threading, soldering or gluing. In certainembodiments of the invention, the diameter of adapter 123 and inlet 114may be substantially equal, albeit with the diameter of one beingslightly larger or smaller than the other to allow the adapter 123 tofit over or inside inlet 114. Optionally, the adapter 123 or inlet 114may assume a substantially circular cross section having an internaldiameter substantially equal to or greater than an external diameter ofthe artery.

Restrictor sleeve 110 and coupler 120 may be connected before, during orafter implantation and deployment onto the arteriovenous junction or thefistula vein. In a preferred embodiment of the invention, coupler 120and restrictor sleeve 110 are connected prior to deployment.Alternatively, restrictor sleeve 110 may be integrally formed as anextension of adapter 123.

Coupler 120 as a whole may be shaped such that, when mount 124 is seatedon the surface of artery AR, the longitudinal axes of adapter 123 andrestrictor sleeve 110 (which typically overlap) are secured at a desiredangle with respect to the longitudinal axis of artery AR. Optionally,the acute angle defined thereby (“the join angle”) is between about 20°and about 60°. In exemplary embodiments of the invention, the join angleis about 40°.

Coupler 120 may be configured to constrain a portion of artery AR towhich it is mounted, or the portion of the fistula vein in the vicinityof the fistula that is substantially contained within the lumen ofadapter 123, to a first constrained shape. In certain embodiments of theinvention, intermediate portion 121 may induce the formation of adesired rounding at the fistula or the nearby blood vessel portions byproviding a fixed rounded contour 126. For example, the intermediateportion 121 may induce a rounding of the blood vessel wall, or to imposea rounded contour, at the acute angle formed at the junction of theconnected blood vessels. The first constrained shape may achieveimproved blood flow at or near the fistula. Such improved flowcharacteristics may include diminished turbulent flow, increasedhemodynamic shear stress, and/or decreasing the average Reynolds numberof the blood flow, e.g., to less than 1500, or to between about 150 toabout 1000.

Coupler 120 may be constructed out of a biocompatible material such asstainless steel, titanium, polymers, or synthetic yarns. The stainlesssteel may comprise, for example, Co—Cr or Ni—Ti alloys. Preferably, thecoupler allows for osmosis at the wall of the first blood vessel tocontinue. As such, the biocompatible material may be semi-permeable, orconstructed with gaps, holes, or the like to keep exposed a substantialportion of the enclosed blood vessel. As such, the coupler may be formedfrom a metal piece having a plurality of slender struts definingopenings therebetween. The metal may be formed by, e.g., machining,casting, forging, laser cutting and like, or a combination thereof. Inexemplary embodiments of the invention, coupler 120 may be laser cutfrom a Ni—Ti alloy solid and include a plurality of slender strutsdefining openings therebetween.

Restrictor sleeve 110 includes an elongated tubular body 111 with anoutlet 113, an inlet 114 and a lumen 112 passing along its length andopen at both ends. Restrictor sleeve 110 is configured to be deployed toensheathe a blood vessel, for example a vein, such that the a portion ofthe blood vessel is enclosed within lumen 112 (or alternatively stated,covered by restrictor sleeve 110). Inlet 114 refers to the open end ofthe restrictor sleeve that is oriented towards (and thus is proximal to)the fistula when the vein is anastomosed to an artery. Outlet 113 refersto the open end of restrictor sleeve 110 that is oriented away from (andthus is distal from) the fistula when the vein is anastomosed to anartery. Typically, after the anastomosis is performed, arterial bloodflow first enters the portion of the vein covered by inlet 114 ofrestrictor sleeve 110, and then exits out of the portion of the veincovered by outlet 113 of restrictor sleeve 110.

Restrictor sleeve 110 may be a few centimeters in length, optionallybetween about 1 cm and about 4 cm or between about 2 cm and about 3 cm.In exemplary embodiments of the invention, restrictor sleeve 110 may beabout 2.5 cm in length. Restrictor sleeve 110 may be positioned on thefistula vein to begin a few millimeters, up to a few centimeters, fromthe fistula along the vein, optionally between about 1 mm and about 50mm, between about 2 mm to about 30 mm or between 5 mm to about 15 mm.

Restrictor sleeve 110 may have a fixed length or can be stretched up toa chosen length, before, after or during deployment over the veinsegment. The width of lumen 112 may be adjusted to constrict the veinsegment to final external boundaries immediately at deployment, or thewidth of lumen 112 may be oversized and designed to allow the veinsegment to expand, up to the final external boundaries restricted by therestrictor sleeve 110. Restrictor sleeve 110 may be configured tosubstantially withstand radial expansion over a predetermined diameter.

Restrictor sleeve 110 may be compressible. Restrictor sleeve 110 may beoperable to be configured in a stressed state that is shorter withrespect to its relaxed length by at least 20%, optionally at least 30%,optionally at least 50%, or higher, or lower, or to an intermediatepercentage. Optionally in addition, the width of lumen 112 may be widerin the stressed state by at least 20%, optionally at least 30%,optionally at least 50%, or higher, or lower, or to an intermediatepercentage.

In some embodiments of the invention, tubular body 111 has acylinder-like (“cylindrical”) shape. In some embodiments of theinvention, tubular body 111 includes a cone-like (“conical”) shape witha cross section that increases with distance from the fistula, thushaving a narrower diameter at inlet 114 and a wider diameter at outlet113. The diameter of outlet 113 may be between about 1.2 and about 1.8times the diameter of inlet 114, or between about 1.3 and about 1.4times the diameter of inlet 114. In exemplary embodiments of theinvention, the diameter of outlet 113 is about 1.4 times the diameter ofinlet 114. As used herein, a cone-like or conical shape is not limitedto a shape that exactly conforms to a geometric cone or a truncatedcone, but to any shape having a cross section that increases withdistance along an axis. The cone-like or conical shape may be a frustum(e.g., a cone, a paraboloid, hyperboloid or a neiloid) or an asymmetricshape.

In some embodiments of the invention, tubular body 111 has a mixedconical/cylindrical shape, with a conical segment proximal to thefistula, followed by a cylindrical segment distal from the fistula.Where tubular body 111 is of the mixed conical/cylindrical shape, theconical segment may comprise between about 50% and about 100% of therestrictor sleeve along its longitudinal axis. Alternatively or incombination, the conical segment may optionally be between about 5 mmand about 35 mm or between about 10 mm and about 25 mm. In exemplaryembodiments of the invention, the conical segment comprises about 60% ofthe restrictor sleeve along its longitudinal axis, with the remaining40% being cylindrical in shape. In exemplary embodiments of theinvention, the conical segment is about 15 mm in length. In exemplaryembodiments of the invention, restrictor sleeve 110 is about 25 mm inlength, having a conical segment of about 15 mm in length and acylindrical segment of about 10 mm in length.

Restrictor sleeve 110 may be constructed out of a biocompatible materialsuch as stainless steel, titanium, polymers, or synthetic yams. Thestainless steel may comprise, e.g., Co—Cr or Ni—Ti alloys. Preferably,restrictor sleeve 110 allows for osmosis at the wall of the first bloodvessel to continue. As such, the biocompatible material may besemi-permeable, or constructed with gaps, holes, or the like to keepexposed a substantial portion of the enclosed blood vessel. In apreferred embodiment of the invention, tubular body 111 is meshed inorder to allow cell ingrowths through its openings and therefore allowimpregnation of the body with the remodeled blood vessel over time. Insome embodiments of the invention, tubular body 111 is braided. In someembodiments of the invention, tubular body 111 is made by intertwiningof three or more wires or fibers, optionally 10 or more intertwinedwires or fibers, optionally thirty or more intertwined wires or fibers.In some embodiments of the invention, wires are used which are made ofstainless steel, optionally of a Ni—Ti alloy. In some embodiments of theinvention, wire diameter is in the range of 1 micron to 1 mm, optionally1 micron to 100 microns, or optionally 30 microns to 60 microns. Inexemplary embodiments of the invention, tubular body 111 comprises abraid having 42 intertwined Ni—Ti alloy wires, each approximately 45microns, or optionally and particularly 43 microns, in diameter.Optionally the braid has a braiding angle (i.e., an angle formed betweentwo adjacent intertwined wires along a longitudinal axis of the braid)when in a relaxed (unstressed) form that is 90° or higher, optionally100° or higher, optionally 120° or higher.

Restrictor sleeve 110 may be configured to constrain the second bloodvessel portion to a desired second constrained shape. The secondconstrained shape may be operable to improve blood flow characteristicsin and around the portion of the fistula vein ensheathed by restrictorsleeve 110. Such improved flow characteristics may include diminishedturbulent flow, increased hemodynamic shear stress, and/or decreasingthe average Reynolds number of the blood flow, e.g., to less than 4000,less than 2000, less than 1500, or to between about 150 and about 1000.

The arteriovenous junction to which fistula join 100 is associated maybe a cephalic vein anastomosed to a radial artery (to form aradiocephalic fistula at the forearm) or to a brachial artery (to form abrachiocephalic fistula at the elbow). The dimensions of fistula join100, including coupler 120 or restrictor sleeve 110, may depend on theexternal diameter of the blood vessels being anastomosed. The externaldiameter of the blood vessels being anastomosed may depend on theparticular blood vessels being used, and on the individual beingtreated. In certain embodiments of the invention, the external diameterof the artery may optionally be between about 2 mm and about 6 mm orbetween about 3 mm and about 5 mm. For example, in case of theradiocephalic fistula, using restrictor sleeve 110 having an inlet 114diameter between 2.4 mm and 3.6 mm and an outlet 113 diameter between2.5 mm and 6.5 mm may be appropriate. Alternatively, in the case of abrachiocephalic fistula, restrictor sleeve 110 having an inlet 114diameter between 3.6 mm and 4.8 mm and an outlet 113 diameter between3.7 mm and 11.7 mm may be appropriate. The dimensions of other portionsor components of the fistula join may be similarly adjusted, inaccordance with the dimensions of the blood vessels.

In certain embodiments of the invention, the portion of the fistula veinproximal to the fistula may be prone to narrowing (for example, due tostenosis and/or neointimal hyperplasia). Fistula join 100 may beoperable to prevent, treat or mitigate stenosis and/or neointimalhyperplasia in the fistula vein at or near the portion of the fistulavein that is externally supported by fistula join 100. Fistula join 100may operable to prevent, treat or mitigate stenosis through, forexample, improving blood flow, reducing turbulence or increasinghemodynamic shear stress, as well as by reducing fistula vein walltension, which may be caused by exposure to arterial blood pressure. Inaddition to improving blood flow and reducing wall tension, fistula join100 may be operable to restrict the expansion of at least the portion ofthe fistula vein within the lumen of coupler 120 or restrictor sleeve110 to within predetermined boundaries. A certain amount of expansion inthe fistula vein may be desired. However, excessive expansion of thefistula vein proximal to the fistula may result in insufficientdownstream peripheral blood flow (for example, steal syndrome, alsoknown as vascular access steal syndrome or dialysis-associated stealsyndrome). As such, fistula join 100 may be operable to prevent, treator mitigate steal syndrome.

FIG. 3 schematically illustrates an exemplary fistula join 200,comprising a restrictor sleeve 210 and a coupler 220. Restrictor sleeve210 may be similar or identical to restrictor sleeve 110. Coupler 220may be similar to coupler 120, or even identical in any or allgeometries and/or features. Optionally, coupler 220 does not include abrace for embracing an artery. In such a case, coupler 220 may beconnectable to the fistula artery and/or to an arteriovenous junctionhaving a fistula by any one or a combination of various methods known inthe art, such as suturing or bonding.

Restrictor sleeve 210 may be shaped as a braided truncated cone made ofintertwined stainless steel (for example, Ni—Ti alloy) wires, having aninlet 212 enclosing a smaller diameter Dv1 and an outlet 211 enclosing agreater diameter Dv2, and a lumen 230 passing therealong sized andconfigured to enclose a fistula vein segment having a length L. Thefistula vein segment ensheathed within restrictor sleeve 210 may be atrisk of developing neointimal hyperplasia and/or stenosis or beexcessively widened to induce steal syndrome. Optionally, length L is 10mm to 50 mm, about 30 mm, about 25 mm, or about 20 mm. The longitudinalaxis of restrictor sleeve 210 may be secured by coupler 220 to maintainan angle a with the longitudinal axis of the artery. Angle a is an acuteangle (i.e., less than) 90°, optionally between 20° and 60°, optionallyabout 40°.

Coupler 220 includes a mount 223, an adapter 222 and an intermediateportion 221. Mount 223 may be shaped and sized with a contour having adiameter Da that is substantially the same as the artery outer diameter,so that it can coincide and nest thereupon. Intermediate portion 221 mayinclude an acutely rounded portion 224 having a radius of curvature R(either variable or fixed). Rounded portion 224 also determines theangle α. Optionally, radius of curvature R is 0.1 mm to 20 mm in length,optionally 0.25 mm to 4 mm, optionally 0.5 mm to 2.5 mm, or higher, orlower, or in an intermediate size.

FIGS. 4A-C schematically illustrate exemplary couplers 300, 400 and 500,which are, respectively, similar or identical to coupler 120, with theexception of differences in respective braces 340, 440 and 540.

FIG. 4A shows a first perspective view (left) and a second perspectiveview (right) of coupler 300. Coupler 300 includes a mount 330 contouredto coincide and nest upon an artery portion having a diameter d1, anadapter 320 comprising a cylindrical shape enclosing a diameter D1 beingequal to or greater than the outer boundaries of a fistula vein segment,and an intermediate portion 310 gradually changing in shape and surfaceorientation between mount 330 and adapter 320. Brace 340 may include twoelastic legs 342 and 344, shown in a nonstressed formation, enclosingdiameter d1 in which they are not in contact. Such a design allows arelatively simpler deploying and securing the coupler 300 to arteries ofslightly different sizes. Legs 342 and 344 may also be bonded or suturedtogether.

FIG. 4B shows a first perspective view (left) and a second perspectiveview (right) of coupler 400. Coupler 400 includes a mount 430 contouredto coincide and nest upon an artery portion having a diameter d2, anadapter 420 comprising a cylindrical shape enclosing a diameter D2 beingequal or greater than outer boundaries of a fistula vein segment, and anintermediate portion 410 gradually changing in shape and surfaceorientation between mount 430 and the adapter 420. Brace 440 may includetwo elastic legs 442 and 444, shown in a nonstressed formation,enclosing a diameter d2 in which they are in contact and closing acomplete circle. Such a design allows a stiffer embracing of an arteryhaving a diameter similar or identical to d2.

FIG. 4C shows a first perspective view (left) and a second perspectiveview (right) of coupler 500. Coupler 500 includes a mount 530 contouredto coincide and nest upon an artery portion having a diameter d3, anadapter 520 comprising a cylindrical shape enclosing a diameter D3 beingequal or greater than outer boundaries of a fistula vein segment, and anintermediate portion 510 gradually changing in shape and surfaceorientation between mount 530 and adapter 520. Brace 540 may include twoelastic legs 542 and 544 shown in a nonstressed formation enclosingdiameter d3 in which they are partly overlaying one on the other. Such adesign allows a stiffer embrace of the artery. Additionally, brace 540may deform the artery portion to a non-circular cross section, which mayimprove blood flow at or near the deformation.

In some alternative embodiments of the invention, any of brace 340, 440and 540, are at least partially plastically deformable and/or can betransformed from elastic conditions to plastic conditions by applyingenough force thereto, so that a user may define a needed enclosingdiameter different from d1, d2, and/or d3, respectively.

Any of coupler 300, 400 and 500 may be connected to a restrictor sleeveto provide a fistula join. Alternatively, a fistula join may include anyof couplers 300, 400 and 500, without a restrictor sleeve.

FIGS. 5A-E schematically illustrate steps that may be included in amethod of deploying and implanting a fistula join 100 (as, for example,described with reference to FIGS. 2A-B). The method may comprise thesteps of: providing a fistula join 100 comprising a coupler 120connected to a restrictor sleeve 110 having a lumen 112; selecting avein VN and an artery AR (FIG. 5A); transecting the vein VN andselecting the vein segment VN leading to the heart (FIG. 5B); passingthe free end of the vein segment VN completely through lumen 112 so thatthe open end of vein segment VN protrudes from coupler 120 (FIG. 5C);anastomosing the open end of vein segment VN to the side of artery AR,as known in common practice, to create an arteriovenous junction havinga fistula (FIG. 5D); and passing fistula join 100 through vein VN toattach coupler 120 to artery AR around the fistula (FIG. 5E).

The above method may include additional steps. For example, the free endof vein segment VN may be trimmed at an angle to facilitate the joiningof vein VN to artery AR at a desired join angle (FIG. 5C).

Additionally or alternatively, if restrictor sleeve 110 is initiallypresented in a compressed state having a greater lumen diameter, thenthe method may include the further step, prior to or following the stepof attaching coupler 120 to artery AR shown in FIG. 5E, of configuringrestrictor sleeve 110 to the non-compressed state having a smaller lumendiameter to firmly enclose vein segment VN in the lumen of restrictorsleeve 110. Additionally or alternatively, restrictor sleeve 110 may besutured and/or bonded in position onto vein segment VN.

Additionally or alternatively, if coupler 120 includes a brace, themethod may include the further step, following the step of attachingcoupler 120 to the artery AR shown in FIG. 5E, of closing the bracearound artery AR. The method may include a yet further step of securingthe closed state of brace 125 with a suture.

In certain alternative embodiments of the invention, the step ofpassing, nesting or securing coupler 120 onto artery AR may be performedbefore the step of performing the anastomosis. Such a procedure allows,for example, for the desired join angle to be secured in advance of aswell as during the performance of anastomosis.

Such an alternative method may comprise the steps of: securing a coupler120 to an artery AR; transecting a vein VN and selecting the veinsegment VN leading to the heart; ensheathing vein segment VN with arestrictor sleeve 110 so that the free end of vein segment VN protrudesfrom inlet 114; connecting inlet 114 to adapter 123 of the coupler 120to construct a fistula join 100; anastomosing the free end of veinsegment VN to the side of artery AR through fistula join 100 to createan arteriovenous junction having a fistula.

Another alternative method may comprise the steps of: securing a coupler120 to an artery AR; connecting the inlet 114 of a restrictor sleeve 110to adapter 123 of coupler 120 to construct a fistula join 100;transecting a vein VN and selecting vein segment VN leading to theheart; ensheathing vein segment VN with a restrictor sleeve 110 so thatthe free end of vein segment VN protrudes from inlet 114 and is apposedto artery AR; anastomosing the free end of vein segment VN to the sideof artery AR through fistula join 100 to create an arteriovenousjunction having a fistula.

Optionally, the ensheathing of vein segment VN with restrictor sleeve110 includes passing restrictor sleeve 110 through a vein VN in acompressed state having a greater lumen diameter, then configuringrestrictor sleeve 110 into the non-compressed state having a smallerlumen diameter that is smaller, larger, or substantially the same as theexternal diameter of the vein VN. Additionally or alternatively,restrictor sleeve 110 may be sutured and/or glued in position over veinsegment VN.

As a further alternative, the methods described above may be performedwithout a restrictor sleeve, for example with a fistula join 100comprising only coupler 120 or coupler 300, 400 or 500, as describedhereinabove. Alternatively, the methods described above may be performedwith a restrictor sleeve, without a coupler.

Any of the above methods may serve to configure any one or anycombination of two or more of the join angle, the first constrainedshape and the second constrained shape (where a restrictor sleeve isused). Additionally or alternatively, any of the above methods may serveto enhance laminar flow of blood through the fistula and/or in at leastone of the fistula artery and fistula vein in the vicinity of thefistula. Additionally or alternatively, any of the above methods mayserve to moderate blood pressure in the fistula artery or fistula veinin the vicinity of the fistula.

As described herein, the fistula join of the embodiments of theinvention serves to configure any one of or any combination of the joinangle, the first constrained shape to second constrained shape (where athe fistula join includes a restrictor sleeve) in the vasculature at orin the vicinity of a fistula to improve blood flow characteristicstherethrough. Such improved blood flow characteristics includediminishing turbulent blood flow, increasing laminar blood flow,increasing hemodynamic shear stress, and/or decreasing the averageReynolds number of the blood flow. As used herein, improved blood flowmay refer to the blood flow exhibiting fewer, smaller or weaker zones ofturbulent/slow flow overall, or fewer, smaller or weaker zones ofturbulent/slow flow located on the luminal surface at the fistula or inthe vein segment in the vicinity of the fistula (for example withinabout 3 cm from the fistula), which may be associated with thedevelopment of stenosis and neointimal hyperplasia.

FIGS. 6A-B, 7A-B, 8A-C and 9 show images of computer simulations ofblood flow from an artery AN through a fistula to a vein VN in avein-end-to-artery-side configuration. Flow velocity is represented in ared-to-blue color gradient, where regions of high velocity/laminar floware shown in red, regions of low velocity/turbulent flow are shown inblue, and regions of intermediate flow are shown in yellow/green. Aspresented herein, the figures have been converted to grayscale, withregions of higher velocity/laminar flow being darker and regions oflower velocity/turbulent flow being lighter.

Various parameters were considered in the simulation, including: bulkblood flow rate (in mL/minute) through vein VN and artery AN on bothsides of the arteriovenous junction; artery diameter, vein diameter(s),arteriotomy length and the join angle (defined as the acute angle atwhich the vein and the artery connect). The vein diameter was optionallyvariable over the distance from the arteriovenous junction. In thesimulations presented, the vein was configured to either be cylindrical,with the diameter remaining constant along the length of the vein, orhave an initial conical segment with the diameter increasing at aconstant rate along the length of the vein for a defined distance CL(alternatively referred to herein as “cone length”) starting from thefistula then become cylindrical. The initial diameter of the vein, atthe circular cross section of the vein in the vicinity of the fistula(e.g., corresponding to the location of line 804 in FIG. 6A), wastypically set to be equal to the diameter of artery AN (e.g.,corresponding to line 802 in FIG. 6A), and the terminal diameter of thevein at and beyond the end of the initial conical segment (e.g., at line806 in FIG. 6A) was set as being a defined multiple of the diameter ofthe artery (ranging from being 1.2 to 2 times the diameter of arteryAN). The artery diameter ranged from about 2.5 mm to about 4 mm,depending on whether a radial artery or a brachial artery was simulated.

Referring now to FIGS. 6A-B and 7A-B, we studied blood flow insimulations of maturing radiocephalic and brachiocephalic junctions. Thematuration of the junctions was represented by: 1) increasing venousflow rate; and 2) increasing vein diameter as expressed as an increasingvein/artery diameter ratio. The radiocephalic junction was configured ashaving an artery diameter 2.9 mm and the brachiocephalic junction wasconfigured as having an artery diameter 4 mm. The vein diameter wasconfigured to increase from 1.2 times the arterial diameter to 2 timesthe arterial diameter. The initial 10 mm of the vein segment mostproximal to the fistula was configured as having a conical shape, withthe remaining vein segment being cylindrical in shape. (The conicalshape may be slight, especially in cases where the differences betweenthe initial and terminal diameters are small. Thus, the conical segmentmay not be readily apparent in the figures.) The arteriotomy was set tobe 5 mm. The join angle was set to be 45°.

We found that, across the two artery types and a range of flow rates,fistulas having a vein/artery diameter ratio of about 1.4 demonstratedthe least turbulence overall. The blood flow in simulated fistulashaving a lower vein/artery diameter ratio, e.g., 1.2, as well as theblood flow in simulated fistulas having a higher vein/artery diameterratio, e.g., 1.6, was in general more turbulent compared to blood flowin simulated fistulas having a vein/artery diameter ratio of 1.4. Inparticular, the simulated blood flow exhibited fewer, smaller and weakerzones of turbulent flow associated with the development of stenosis andneointimal hyperplasia, i.e., located on the luminal surface at thefistula or in the vein segment proximal to the fistula (for example,within about 3 cm from the fistula).

FIGS. 6A-B show exemplary images of blood flow through a simulation of adeveloping radiocephalic junction. In the transition between FIG. 6A andFIG. 6B, the vein/artery diameter ratio changed from 1.2 to 1.4 with theother parameters remaining the same (including the blood flow rate invein VN, which was maintained at 265 mL/minute). Referring to FIG. 6A,the initial vein diameter, e.g., at line 804 is equal to the arterydiameter, e.g., at line 802, and the terminal vein diameter, e.g., atline 806, is 1.2 times the artery diameter. Referring to FIG. 6B, theinitial vein diameter, e.g., at line 814, is equal to the arterydiameter, e.g., at line 812, and the terminal vein diameter, e.g., atline 816 is 1.4 times the artery diameter.

The improvement of blood flow in the junction having a vein/arterydiameter ratio of 1.4 (FIG. 6B) compared to a vein/artery diameter ratioof 1.2 (FIG. 6A), can been seen by the reduction in the size of regionsof turbulent blood flow (light) combined with the increase in size ofregions of laminar blood flow (dark). This improvement in blood flow isparticularly apparent where turbulent region 704 along the lumen of veinVN having a vein/artery diameter ratio of 1.2 (FIG. 6A) is larger thanthe corresponding turbulent region 707 along the lumen of vein VN havinga vein/artery diameter ration of 1.4 (FIG. 6B). A similar reduction inturbulent flow is apparent when comparing the size of turbulent flowregion turbulent region 702 (FIG. 6A) with corresponding turbulentregion 706 (FIG. 6B).

Having a conical segment in the initial portion of the fistula vein witha larger vein/artery diameter ratio does not necessarily improve bloodflow through the arteriovenous junction. FIGS. 7A-B show the samesimulated radiocephalic junction exhibiting increased turbulence whenthe vein/artery ratio increased from 1.4 to 1.6, while the otherparameters remained unchanged (including the blood flow rate at vein VN,which was maintained at 495 mL/minute). Referring to FIG. 7A, theinitial vein diameter, e.g., at line 824, is equal to the arterydiameter, e.g., at line 822, and the terminal vein diameter, e.g., atline 826, is 1.4 times the artery diameter. Referring to FIG. 7B, theinitial vein diameter, e.g., at line 834, is equal to the arterydiameter, e.g., at line 832, and the terminal vein diameter, e.g., atline 836 is 1.6 times the artery diameter.

The degradation of blood flow in the junction having a vein/arterydiameter ratio of 1.6 (FIG. 7B) compared to a vein/artery diameter ratioof 1.4 (FIG. 7A), is particularly apparent where turbulent region 708along the lumen of vein VN having a vein/artery diameter ratio of 1.4(FIG. 6A) is smaller than the corresponding turbulent region 710 alongthe lumen of vein VN having a vein/artery diameter ration of 1.6 (FIG.6B).

We also found that a conical segment having a length of about 15 mm wasparticularly beneficial, across a range of other conditions such asartery diameter, blood flow rate and vein/artery diameter ratios, inimproving blood flow through simulated arteriovenous junctions.Referring now to FIGS. 8A-C, we tested four different lengths of theinitial conical segment: 0 mm (completely cylindrical in shape; notshown), 15 mm (FIG. 8A; cone length CL1 defined by lines 842 and 844),20 mm (FIG. 8B; cone length CL2 defined by lines 862 and 864) and 25 mm(FIG. 8C; cone length CL3 defined by lines 882 and 884). The simulatedjunctions were configured as a brachiocephalic junction having the samefollowing parameters: an artery diameter 3.5 mm, a vein/artery diameterratio of 1.29 (with the terminal vein diameter after the conical segmentbeing 4.5 mm), a join angle 40°, an arteriotomy length 5 mm, and aninitial arterial blood flow rate 200 mL/minute. Vein segment VN beyondthe conical segment was configured to be cylindrical in shape. Theimprovement in blood flow in vein VN having the 15 mm conical region(FIG. 8A) is particularly apparent at turbulent region (light) region712, which was smaller than corresponding turbulent region 714 of FIG.8B where the conical region is 20 mm, and also smaller thancorresponding turbulent region 716 of FIG. 8C where the conical regionis 25 mm.

Further simulations, similarly performed, demonstrated that a fistulajoin angle of about 40° was particularly beneficial in reducingturbulent blood flow. That is, simulated junctions having a join angle40°, across various conditions such as artery diameter, blood flow rateand vein/artery diameter ratios, generally demonstrated less turbulentblood flow when compared to simulated junctions having a join angle of20° or 60°.

Referring now to FIG. 9 , we also generated a simulated junction in aconventional configuration having a join angle 15° and a fullycylindrical vein (without an initial conical segment), which is one ofvarious configurations that an arteriovenous junction may typically takewithout implantation of structural supports. The remaining parametersgenerally match the simulations shown in FIGS. 8A-C: an artery diameter3.5 mm, a vein/artery diameter ratio of 1.29 (with the vein diameterbeing 4.5 mm), an arteriotomy length 6 mm and an initial arterial bloodflow rate 200 mL/minute. This conventional junction exhibited a higherlevel of turbulent flow overall, and further exhibited two focusedregions of turbulent flow 718, 720 juxtaposing with the fistula. Assuch, any one of the above-described geometrical features, such as ajoin angle 40° or an initial conical segment in the vein will improveblood flow at or near an arteriovenous fistula over conventionalconditions.

Based on the simulation studies as described above, certain embodimentsof the invention provide for a fistula join operable to shape orconstrain the fistula or the surrounding vasculature to have one or moreof the following preferred parameters: a join angle of about 40°; avein/artery diameter ratio of about 1.4; or a fistula vein segment beingconical in shape at the initial approximately 15 mm from the fistula,then optionally being cylindrical in shape.

Certain embodiments of the invention further provide for a preferredfistula join comprising: a restrictor sleeve having a mixedconical/cylindrical shape, the initial segment of about 15 mm startingfrom the inlet being conical and the remainder being cylindrical, andthe outlet diameter being larger than the inlet diameter by a factor ofabout 1.4; and a coupler having an adapter configured to connect withthe inlet and secure the restrictor sleeve at a join angle of about 40°.

In the description and claims of the present application, each of theverbs, “comprise” “include” and “have”, and conjugates thereof, are usedto indicate that the object or objects of the verb are not necessarily acomplete listing of components, elements or parts of the subject orsubjects of the verb.

Descriptions of embodiments of the invention in the present applicationare provided by way of example and are not intended to limit the scopeof the invention. The described embodiments comprise different features,not all of which are required in all embodiments of the invention. Someembodiments utilize only some of the features or possible combinationsof the features. Variations of embodiments of the invention that aredescribed, and embodiments of the invention comprising differentcombinations of features noted in the described embodiments, will occurto persons of the art. The scope of the invention is limited only by theclaims.

The invention claimed is:
 1. An apparatus for configuring first andsecond blood vessels, wherein the first blood vessel is connected to asecond blood vessel, creating a fistula, the apparatus comprising: acoupler with a first side that seats on and couples to an externalsurface of the first blood vessel surrounding the fistula, the couplerincluding a lumen connecting the first side of the coupler at thefistula to a second side of the coupler; and a sleeve having a lumen, afirst end of the sleeve connecting to the second side of the coupler,thereby connecting the lumen of the sleeve and the lumen of the coupler,the lumen of the sleeve ensheathing at least a portion of the secondblood vessel, wherein the lumen of the coupler and the lumen of thesleeve together form a structure for holding the second blood vessel ata substantially constant angle with respect to the first blood vessel,and the coupler is configured to impose a first constrained shape on thefirst blood vessel and the sleeve is configured to impose a secondconstrained shape on the second blood vessel, the first constrainedshape having a first diameter (D₁) and the second constrained shapebeing inclusive of a conical segment with a diameter that increasescontinuously, as a function of distance from the fistula, from a seconddiameter (D₂) proximal to the fistula to a third diameter (D₃) distalfrom the fistula, wherein the first and second diameters are equal(D₁=D₂) and a diameter ratio of the third to first diameters (D₃:D₁) isin a range from about 1.2 to about 1.6.
 2. The apparatus of claim 1,wherein the substantially constant angle between the first blood vesseland the second blood vessel is between about 20° and about 60°.
 3. Theapparatus of claim 1, wherein the substantially constant angle betweenthe first blood vessel and the second blood vessel is about 40°.
 4. Theapparatus of claim 1, wherein the substantially constant angle betweenthe first blood vessel and the second blood vessel is about 50°.
 5. Theapparatus of claim 1, wherein the coupler is configured to impose arounded contour to the first blood vessel and the second blood vessel,in proximity to the fistula.
 6. The apparatus of claim 1, wherein thefirst blood vessel is an artery and the second blood vessel is a vein.7. The apparatus of claim 1, wherein the diameter ratio (D₂:D₁) is about1.4.
 8. An apparatus for configuring first and second blood vessels,wherein the first blood vessel is connected to a second blood vessel,creating a fistula, the apparatus comprising: a coupler with a firstside that seats on and couples to an external surface of the first bloodvessel surrounding the fistula, the coupler including a lumen connectingthe first side of the coupler at the fistula to a second side of thecoupler; and a sleeve having a lumen, a first end of the sleeveconnecting to the second side of the coupler, thereby connecting thelumen of the sleeve and the lumen of the coupler, the lumen of thesleeve and the lumen of the coupler together ensheathing at least aportion of the second blood vessel, thereby forming a structure forholding the second blood vessel at a substantially constant angle withrespect to the first blood vessel, wherein the coupler is configured toimpose a first constrained shape on the first blood vessel and thesleeve is configured to impose a second constrained shape on the secondblood vessel, the first constrained shape having a first diameter (D₁)and the second constrained shape being inclusive of a conical segmentwith a diameter that increases continuously, as a function of distancefrom the fistula, from a second diameter (D₂) proximal to the fistula toa third diameter (D₃) distal from the fistula, wherein the first andsecond diameters are equal (D₁=D₂) and a diameter ratio of the third tofirst diameters (D₃:D₁) is in a range from about 1.2 to about 1.6. 9.The apparatus of claim 8, wherein the substantially constant anglebetween the first blood vessel and the second blood vessel is betweenabout 20° and about 60°.
 10. The apparatus of claim 8, wherein thesubstantially constant angle between the first blood vessel and thesecond blood vessel is about 40°.
 11. The apparatus of claim 8, whereinthe substantially constant angle between the first blood vessel and thesecond blood vessel is about 50°.
 12. The apparatus of claim 8, whereinthe coupler is configured to impose a rounded contour to the first bloodvessel and the second blood vessel, in proximity to the fistula.
 13. Theapparatus of claim 8, wherein the first blood vessel is an artery andthe second blood vessel is a vein.
 14. The apparatus of claim 8, whereinthe diameter ratio (D₂:D₁) is about 1.4.
 15. A method for configuringfirst and second blood vessels, wherein the first blood vessel isconnected to a second blood vessel, creating a fistula, the methodcomprising the steps of: seating and coupling a first side of a couplerto an external surface of the first blood vessel surrounding thefistula, the coupler including a lumen connecting the first side of thecoupler at the fistula to a second side of the coupler; and connecting afirst side of a sleeve having a lumen to the second side of the coupler,thereby connecting the lumen of the sleeve and the lumen of the coupler,the lumen of the sleeve ensheathing at least a portion of the secondblood vessel, wherein the lumen of the coupler and the lumen of thesleeve together form a structure for holding the second blood vessel ata substantially constant angle with respect to the first blood vessel,and the coupler is configured to impose a first constrained shape on thefirst blood vessel and the sleeve is configured to impose a secondconstrained shape on the second blood vessel, the first constrainedshape having a first diameter (D₁) and the second constrained shapebeing inclusive of a conical segment with a diameter that increasescontinuously, as a function of distance from the fistula, from a seconddiameter (D₂) proximal to the fistula to a third diameter (D₃) distalfrom the fistula, wherein the first and second diameters are equal(D₁=D₂) and a diameter ratio of the third to first diameters (D₃:D₁) isin a range from about 1.2 to about 1.6.
 16. The method of claim 15,wherein the substantially constant angle between the first blood vesseland the second blood vessel is between about 20° and about 60°.
 17. Themethod of claim 15, wherein the substantially constant angle between thefirst blood vessel and the second blood vessel is about 40°.
 18. Themethod of claim 15, wherein the substantially constant angle between thefirst blood vessel and the second blood vessel is about 50°.
 19. Themethod of claim 15, wherein the coupler is configured to impose arounded contour to the first blood vessel and the second blood vessel,in proximity to the fistula.
 20. The method of claim 15, wherein thediameter ratio (D₂:D₁) is about 1.4.
 21. A method for configuring firstand second blood vessels, wherein the first blood vessel is connected toa second blood vessel, creating a fistula, the method comprising thesteps of: seating and coupling a first side of a coupler to an externalsurface of the first blood vessel surrounding the fistula, the couplerincluding a lumen connecting the first side of the coupler at thefistula to a second side of the coupler; and connecting a first end of asleeve having a lumen to the second side of the coupler, therebyconnecting the lumen of the sleeve and the lumen of the coupler, thelumen of the sleeve and the lumen of the coupler together ensheathing atleast a portion of the second blood vessel, thereby forming a structurefor holding the second blood vessel at a substantially constant anglewith respect to the first blood vessel, wherein the coupler isconfigured to impose a first constrained shape on the first blood vesseland the sleeve is configured to impose a second constrained shape on thesecond blood vessel, the first constrained shape having a first diameter(D₁) and the second constrained shape being inclusive of a conicalsegment with a diameter that increases continuously, as a function ofdistance from the fistula, from a second diameter (D₂) proximal to thefistula to a third diameter (D₃) distal from the fistula, wherein thefirst and second diameters are equal (D₁=D₂) and a diameter ratio of thethird to first diameters (D₃:D₁) is in a range from about 1.2 to about1.6.
 22. The method of claim 21, wherein the substantially constantangle between the first blood vessel and the second blood vessel isbetween about 20° and about 60°.
 23. The method of claim 21, wherein thesubstantially constant angle between the first blood vessel and thesecond blood vessel is about 40°.
 24. The method of claim 21, whereinthe substantially constant angle between the first blood vessel and thesecond blood vessel is about 50°.
 25. The method of claim 21, whereinthe coupler is configured to impose a rounded contour to the first bloodvessel and the second blood vessel, in proximity to the fistula.
 26. Theapparatus of claim 21, wherein the diameter ratio (D₂:D₁) is about 1.4.